tbuckley/cabot-search huggingface dataset:
Discovering a trans-omics biomarker signature that predisposes high risk diabetic patients to diabetic kidney disease
Authors: I-Wen Wu, Tsung-Hsien Tsai, Chi-Jen Lo, Yi-Ju Chou, Chi-Hsiao Yeh, Yun-Hsuan Chan, Jun-Hong Chen, Paul Wei-Che Hsu, Heng-Chih Pan, Heng-Jung Hsu, Chun-Yu Chen, Chin-Chan Lee, Yu-Chiau Shyu, Chih-Lang Lin, Mei-Ling Cheng, Chi-Chun Lai, Huey-Kang Sytwu, Ting-Fen Tsai
Journal: npj Digital Medicine (2022)

Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein-protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.
Pure (acute) erythroid leukemia: morphology, immunophenotype, cytogenetics, mutations, treatment details, and survival data among 41 Mayo Clinic cases
Authors: Kaaren K. Reichard, Ayalew Tefferi, Maymona Abdelmagid, Attilio Orazi, Christina Alexandres, Joanna Haack, Patricia T. Greipp
Journal: Blood Cancer Journal (2022)

Abstract Pure erythroid leukemia (PEL), also known as acute erythroid leukemia (AEL), is recognized as a distinct morphologic entity by both the 2016 and 2022 World Health Organization (WHO) classification system. By contrast, the 2022 International Consensus Classification (ICC) includes PEL under a broader category of “acute myeloid leukemia with mutated TP53 ”. We identified 41 Mayo Clinic cases of PEL (mean age 66 years, range 27–86; 71% males) and provide a comprehensive account of bone marrow morphology, immunophenotype, cytogenetic and mutation profiles. PEL was primary in 14 cases, therapy-related in 14, secondary in 12, and undetermined in one. All cases expressed biallelic TP53 alterations, including TP53 deletion/single TP53 mutation (68%), two TP53 mutations (29%) or two TP53 deletions (3%); additional mutations were infrequent. Karyotype was complex in all cases and monosomal in 90%. Treatment details were available in 29 patients: hypomethylating agent (HMA) alone ( n = 5), HMA + venetoclax ( n = 12), intensive chemotherapy ( n = 4), supportive care/other ( n = 8); no responses or allogeneic stem cell transplants were documented, and all patients died at a median 1.8 months (range 0.2–9.3). The current study highlights a consistent and reproducible set of morphologic and genetic characteristics that identify PEL as a distinct AML variant whose dismal prognosis requires urgent attention.
Synaptic pruning through glial synapse engulfment upon motor learning
Authors: Yosuke M. Morizawa, Mami Matsumoto, Yuka Nakashima, Narumi Endo, Tomomi Aida, Hiroshi Ishikane, Kaoru Beppu, Satoru Moritoh, Hitoshi Inada, Noriko Osumi, Eiji Shigetomi, Schuichi Koizumi, Guang Yang, Hirokazu Hirai, Kohichi Tanaka, Kenji F. Tanaka, Nobuhiko Ohno, Yugo Fukazawa, Ko Matsui
Journal: Nature Neuroscience (2022)
Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool
Authors: Carmen Romero-Molina, Francesca Garretti, Shea J. Andrews, Edoardo Marcora, Alison M. Goate
Journal: Neuron (2022)

Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer's disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting relevant genes identified in the latest AD genetics and genomics studies, and describe how they may contribute to AD pathogenesis. Investigating the functional impact of AD-associated variants and genes in microglia is essential for elucidating disease risk mechanisms and developing effective therapeutic approaches.
Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl− concentration in airway epithelium
Authors: Zhuo-Er Qiu, Lei Chen, Xiao-Chun Hou, Jie Sheng, Jian-Bang Xu, Jia-Wen Xu, Dong-Dong Gao, Ze-Xin Huang, Tian-Lun Lei, Zi-Yang Huang, Lei Peng, Hai-Long Yang, Qin-Hua Lin, Yun-Xin Zhu, Wei-Jie Guan, Zhao-Rong Lun, Wen-Liang Zhou, Yi-Lin Zhang
Journal: Journal of Infection (2022)
2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease
Authors: Eric M. Isselbacher, Ourania Preventza, James Hamilton Black III, John G. Augoustides, Adam W. Beck, Michael A. Bolen, Alan C. Braverman, Bruce E. Bray, Maya M. Brown-Zimmerman, Edward P. Chen, Tyrone J. Collins, Abe DeAnda, Christina L. Fanola, Leonard N. Girardi, Caitlin W. Hicks, Dawn S. Hui, William Schuyler Jones, Vidyasagar Kalahasti, Karen M. Kim, Dianna M. Milewicz, Gustavo S. Oderich, Laura Ogbechie, Susan B. Promes, Elsie Gyang Ross, Marc L. Schermerhorn, Sabrina Singleton Times, Elaine E. Tseng, Grace J. Wang, Y. Joseph Woo
Journal: Journal of the American College of Cardiology (2022)
Microglia states and nomenclature: A field at its crossroads
Authors: Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brône, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J.L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta González, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valérie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray
Journal: Neuron (2022)
High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial
Authors: Kristoffer S. Hansen, Trine H. Mogensen, Jane Agergaard, Berit Schiøttz-Christensen, Lars Østergaard, Line K. Vibholm, Steffen Leth
Journal: The Lancet Regional Health - Europe (2022)

Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms. In this placebo-controlled, double-blind, 2 × 2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for 6 weeks, with crossover treatment after a 4-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the 6-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment. From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods – 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43.06 (95% CI: 40.18; 45.94), and the mean EQ-5D health index was 0.66 (95% CI: 0.64; 0.68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0.01; 95% CI: −0.02; 0.04; p = 0.45) or the change in PCC-related symptom score (with a mean difference of −1.18; 95% CI: −3.54; 1.17; p = 0.32). Based on self-reported data, CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo. However, we observed a significant spontaneous improvement on both scores regardless of treatment during 20 weeks observation. Placebo and CoQ10 capsules were provided by Pharma Nord, and the trial was supported by grants from the Novo Nordisk Foundation (NNF21OC0066984). This trial is registered with EudraCT, 2020-005961-16 and ClinicalTrials.gov, NCT04960215. The trial is completed.
Corrigendum to “Quantum dots: The cutting-edge nanotheranostics in brain cancer management” [Journal of Controlled Release, Volume 350 (2022) Pages 698–715]
Authors: Pratik Chakraborty, Sabya Sachi Das, Abhijit Dey, Apala Chakraborty, Chiranjib Bhattacharyya, Ramesh Kandimalla, Biswajit Mukherjee, Abilash Valsala Gopalakrishnan, Sandeep Kumar Singh, Shubham Kant, Parma Nand, Shreesh Ojha, Pravir Kumar, Niraj Kumar Jha, Saurabh Kumar Jha, Saikat Dewanjee
Journal: Journal of Controlled Release (2022)
Combining PD-L1 blockade with immunogenic cell death induced by AIE photosensitizer to improve antitumor immunity
Authors: Jianqing Li, Jun Dai, Zeyan Zhuang, Zijuan Meng, Jing-Jing Hu, Xiaoding Lou, Fan Xia, Zujin Zhao, Ben Zhong Tang
Journal: Biomaterials (2022)
Interventions to improve health and the determinants of health among sex workers in high-income countries: a systematic review
Authors: Luke Johnson, Lucy C Potter, Harriet Beeching, Molly Bradbury, Bella Matos, Grace Sumner, Lorna Wills, Kitty Worthing, Robert W Aldridge, Gene Feder, Andrew C Hayward, Neha Pathak, Lucy Platt, Al Story, Binta Sultan, Serena A Luchenski
Journal: The Lancet Public Health (2022)
Self-amplified ROS production from fatty acid oxidation enhanced tumor immunotherapy by atorvastatin/PD-L1 siRNA lipopeptide nanoplexes
Authors: Yan Gao, Zilin Song, Li Jia, Yi Tang, Chengcheng Wang, Xiuli Zhao, Haiyang Hu, Dawei Chen, Mingxi Qiao
Journal: Biomaterials (2022)
Increased social identification is linked with lower depressive and anxiety symptoms among ethnic minorities and migrants: A systematic review and meta-analysis
Authors: Kristine Brance, Vasileios Chatzimpyros, Richard P. Bentall
Journal: Clinical Psychology Review (2022)

Evidence suggests that social identities, which provide purpose and a sense of belonging to the social world, promote resilience against psychological strain and protect well-being. This is especially important in ethnic minorities, who experience exclusion and discrimination from the majority group, and in migrant populations where adverse experiences, such as prejudice, disconnection from previous identities and issues of integration into the host country, negatively impact well-being. Drawing from the social identity theory, a meta-analysis was conducted examining the influence of group memberships and sense of belonging on ethnic minority and migrant mental health (depression and anxiety). The final search on three databases (i.e., PubMed, PsycINFO, Web of Science) was conducted on August 9th, 2022, identifying 3236 citations before removing any duplicates within and between databases. Across the 74 studies that met the inclusion criteria for the meta-analysis, increased social identification (ethnic, national and other types of identification) was associated with low psychological symptoms. We found that social identification is protective against common psychological disorders but with small effect sizes for depression (r = - 0.09, CI = [- 0.12; - 0.06]) and anxiety (r = - 0.08, CI [- 0.12; - 0.03]). Results are discussed with regard to the role that social context plays on ethnic minority and migrant mental health and the importance of facilitating migrant integration with the host society after displacement.
Mitochondrial signal transduction
Authors: Martin Picard, Orian S. Shirihai
Journal: Cell Metabolism (2022)

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS). In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology. This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.
Rhamnan sulfate reduces atherosclerotic plaque formation and vascular inflammation
Authors: Nikita P. Patil, Almudena Gómez-Hernández, Fuming Zhang, Limary Cancel, Xu Feng, Lufeng Yan, Ke Xia, Eri Takematsu, Emily Y. Yang, Victoria Le, Megan E. Fisher, Agueda Gonzalez-Rodriguez, Carmelo Garcia-Monzon, James Tunnell, John Tarbell, Robert J. Linhardt, Aaron B. Baker
Journal: Biomaterials (2022)
Challenges in TB research
Authors: Thomas J. Scriba, Ryan Dinkele, Digby F. Warner, Valerie Mizrahi
Journal: The Journal of Experimental Medicine (2022)

Tuberculosis (TB) is an infectious disease bedeviled by complexity. This poses myriad challenges for a research ecosystem organized around specialist host- and/or pathogen-focused thrusts. Here, we highlight the key challenges and their implications for developing new tools to control TB.
Quantifying the effect of inequitable global vaccine coverage on the COVID-19 pandemic
Journal: Nature Medicine (2022)

Quantifying the effect of inequitable global vaccine coverage on the COVID-19 pandemicWe used a global mathematical model simulating different scenarios to study the effects of increased COVID-19 vaccine equity during 2021.Our results indicate that vaccine nationalism leads to increased infections and mortality worldwide, and by favoring the emergence of new viral variants, in the long term it may adversely affect all countries.
Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss
Authors: Fateeha Furqan, Nirav N. Shah
Journal: Annual Review of Medicine (2022)

Chimeric antigen receptor (CAR) modified T cell therapy has transformed the management of relapsed/refractory B cell malignancies. Despite high overall response rates, relapse post CAR T treatment remains a clinical challenge. Loss of target antigen, specifically CD19, is one well-defined mechanism of disease relapse. The mechanism of CD19 loss and which patients are at higher risk of CD19 loss remain poorly understood. To overcome CD19 loss, CARs targeting multiple antigens are being tested in clinical trials. CD19/20 and CD19/22 bispecific CARs demonstrate cytotoxicity against CD19-negative cells in preclinical studies. These CARs have also shown efficacy, safety, and a relatively low rate of CD19-negative relapse in phase I trials. These small studies suggest that multispecific CAR T cells can deprive lymphomas of escape via antigen loss. However, the selection of an ideal target, the right CAR construct, and whether these multispecific CARs can induce long-term remissions are still under investigation.
Climate change, health, and discrimination: action towards racial justice
Authors: Thilagawathi Abi Deivanayagam, Sujitha Selvarajah, Jason Hickel, Renzo R Guinto, Priscila de Morais Sato, Jon Bonifacio, Sonora English, Mita Huq, Rita Issa, Hans Mulindwa, Heizal Patricia Nagginda, Chetna Sharma, Delan Devakumar
Journal: The Lancet (2022)
Cytomegalovirus Therapy: Role of Letermovir in Prophylaxis and Treatment in Transplant Recipients
Authors: Jennifer L. Saullo, Rachel A. Miller
Journal: Annual Review of Medicine (2022)

Cytomegalovirus (CMV) is a common viral pathogen in the transplant population and is associated with significant morbidity and mortality. CMV prevention is paramount; however, selecting the best preventive strategy depends on many factors including donor–recipient CMV serostatus, transplant-specific risks, antiviral toxicities and cost. Novel CMV therapeutics such as letermovir (LTV) are desperately needed to optimize CMV management. Uniquely among CMV antiviral therapies, LTV inhibits the viral terminase complex in the CMV DNA synthesis pathway and disrupts viral genome packaging. Further, it lacks side effects frequently associated with other CMV antiviral therapies and evades common mechanisms of resistance. LTV is approved by the US Food and Drug Administration for CMV prevention in adult CMV-seropositive hematopoietic cell transplant recipients but is increasingly applied off-label for prophylaxis and treatment. This review summarizes important concepts of CMV management in transplantation, with a specific focus on LTV pharmacology and clinical experience to date alongside future prospects for its application.
S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters
Authors: Michihito Sasaki, Koshiro Tabata, Mai Kishimoto, Yukari Itakura, Hiroko Kobayashi, Takuma Ariizumi, Kentaro Uemura, Shinsuke Toba, Shinji Kusakabe, Yuki Maruyama, Shun Iida, Noriko Nakajima, Tadaki Suzuki, Shinpei Yoshida, Haruaki Nobori, Takao Sanaki, Teruhisa Kato, Takao Shishido, William W. Hall, Yasuko Orba, Akihiko Sato, Hirofumi Sawa
Journal: Science Translational Medicine (2022)

In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo. Here, we show that oral administration of S-217622 (ensitrelvir), an inhibitor of SARS-CoV-2 main protease (Mpro; also known as 3C-like protease), decreases viral load and ameliorates disease severity in SARS-CoV-2-infected hamsters. S-217622 inhibited viral proliferation at low nanomolar to submicromolar concentrations in cells. Oral administration of S-217622 demonstrated favorable pharmacokinetic properties and accelerated recovery from acute SARS-CoV-2 infection in hamster recipients. Moreover, S-217622 exerted antiviral activity against SARS-CoV-2 variants of concern, including the highly pathogenic Delta variant and the recently emerged Omicron BA.5 and BA.2.75 variants. Overall, our study provides evidence that S-217622, an antiviral agent that is under evaluation in a phase 3 clinical trial (clinical trial registration no. jRCT2031210350), has remarkable antiviral potency and efficacy against SARS-CoV-2 and is a prospective oral therapeutic option for COVID-19.